- Email: [email protected]
Lessons for bioprostheses learned from the biology of natural valves
Cardiovasc Pathol Vol. 5, No. 5 September/October 1996:286-302
ABSTRACTS
STRUCTURE-FUNCTION CORRELATIONSIN TISSUE HEART VALVES Frederick J. Schoen,Brigham and Women’sHospital and Harvard Medical School, Boston, MA This presentationsummarize-s the mechanismsof both failure and successin tissueheart valves, including glutaraldehyde-pretreated porcine and pericardial bioprosthesesand cryopreservedallograft aortic valves. Dystrophic calcification-inducedstructural dysfunction of porcine aortic valve bioprosfheses accountsfor > 50% failure in 12-15 years. Experimentaland clinical investigationshave consistentlydemonstratedthat the mechanismof calcification is initially cell-mediated,with calcium phosphatecrystals nucleatedat the transplantedcell membranesand in organelles;collagencalcification occurs later. The critical cellular event is reaction of calcium-containingextracellular fluid with the membrane-associated phosphorus..In cells madenon-viable by glutaraldehydefixation or autolysis, energy is unavailable, membranesare disrupted and calcium exclusion is impaired. The major mechanismof failure in pericurdiul bioprosrheses is design-relatedtissue tearing, often with a strong componentof abrasionof tissue againststent components. Calcification assumesa less important role. In cryopreserved allograft valves, procurement-related ischemiaand perhapsfreeze/thawdamagecontributesto loss of normal architecturaldetail and endothelial and deepconnectivetissue cells. Inflammatory cell infiltration is generally limited, suggestingthat immunological rejection plays an unimportantrole in inhibiting the successof theseprostheses. Since these valves are morphologically non-viable, the structural basisfor function seemsprimarily related to a preserved,though altered, collagenoussubstructure,and such valves are unlikely to have the capacity to grow, remodel, or exhibit active metabolicfunctions. Interestingly and in contrast, uortic valves from orthofopic whole heart transplants maintain near normal overall architecture,endothelial cells, and deep connectivetissue cells. Preliminary data suggestthat valve viability can be maintainedin aufologous pulmonary valves transplanted to the aortic site (Rossprocedure).
LESSONSFOR BIOPROSTHESESLEARNED FROM THE BIOLOGY OF NATURAL VALVES Lois C. Armiger, University of Auckland School of Medicine, Auckland, NEW ZEALAND At the microscopiclevel, the apparently simple leaflet tissue of the natural semilunar valve is a highly organisedstructureand the cell population is closely integratedwith its major products:collagen, e&in, andproteoglycanmatrix. The matrix not only contributesto structuralintegrity but is essentialfor optimal cellular activity and survival. Whenthe naturalvalve is usedasan allqraft the leafletsgenerallylosecells and matrix in the short-termand the chief mechanicalcomponent,collagen, progressivelybut relatively slowly degeneratesasa consequence.Cells and matrix are both adverselyaffectedby prolongedautolysis and cell viability, in particular, by disinfection and storageproceduresalso. Hence, in cadaver-derived valves preparedfor grafting these important componentsmay already be low or absentat the time of implantation. In allografts explantedafter severaIyears, any original donor cells which have survived in the leafletshave usually not maintaineda normal tissuearchitecture. Bearingin mind the possibility that the histology of allograftedvalves which have required replacementmay differ from that of grafts which are still in place and functioning well, the abovefacts neverthelesscast doubt on the alleged importance of pre-implantationcell viability per se for this type of bioprostbesis. Since a percentageof &grafts known to be completely non-viable at implantation have survived for as long as 20-30 years, factors unrelatedto the persistenceof a donor cell population needto be consideredin future research. Supportedby the Health ResearchCouncil of NZ, the Auckland Medical ResearchFoundationand the NZ Lotteries Board.
289
ABSTRACTS
STRUCTURE-FUNCTION CORRELATIONSIN TISSUE HEART VALVES Frederick J. Schoen,Brigham and Women’sHospital and Harvard Medical School, Boston, MA This presentationsummarize-s the mechanismsof both failure and successin tissueheart valves, including glutaraldehyde-pretreated porcine and pericardial bioprosthesesand cryopreservedallograft aortic valves. Dystrophic calcification-inducedstructural dysfunction of porcine aortic valve bioprosfheses accountsfor > 50% failure in 12-15 years. Experimentaland clinical investigationshave consistentlydemonstratedthat the mechanismof calcification is initially cell-mediated,with calcium phosphatecrystals nucleatedat the transplantedcell membranesand in organelles;collagencalcification occurs later. The critical cellular event is reaction of calcium-containingextracellular fluid with the membrane-associated phosphorus..In cells madenon-viable by glutaraldehydefixation or autolysis, energy is unavailable, membranesare disrupted and calcium exclusion is impaired. The major mechanismof failure in pericurdiul bioprosrheses is design-relatedtissue tearing, often with a strong componentof abrasionof tissue againststent components. Calcification assumesa less important role. In cryopreserved allograft valves, procurement-related ischemiaand perhapsfreeze/thawdamagecontributesto loss of normal architecturaldetail and endothelial and deepconnectivetissue cells. Inflammatory cell infiltration is generally limited, suggestingthat immunological rejection plays an unimportantrole in inhibiting the successof theseprostheses. Since these valves are morphologically non-viable, the structural basisfor function seemsprimarily related to a preserved,though altered, collagenoussubstructure,and such valves are unlikely to have the capacity to grow, remodel, or exhibit active metabolicfunctions. Interestingly and in contrast, uortic valves from orthofopic whole heart transplants maintain near normal overall architecture,endothelial cells, and deep connectivetissue cells. Preliminary data suggestthat valve viability can be maintainedin aufologous pulmonary valves transplanted to the aortic site (Rossprocedure).
LESSONSFOR BIOPROSTHESESLEARNED FROM THE BIOLOGY OF NATURAL VALVES Lois C. Armiger, University of Auckland School of Medicine, Auckland, NEW ZEALAND At the microscopiclevel, the apparently simple leaflet tissue of the natural semilunar valve is a highly organisedstructureand the cell population is closely integratedwith its major products:collagen, e&in, andproteoglycanmatrix. The matrix not only contributesto structuralintegrity but is essentialfor optimal cellular activity and survival. Whenthe naturalvalve is usedasan allqraft the leafletsgenerallylosecells and matrix in the short-termand the chief mechanicalcomponent,collagen, progressivelybut relatively slowly degeneratesasa consequence.Cells and matrix are both adverselyaffectedby prolongedautolysis and cell viability, in particular, by disinfection and storageproceduresalso. Hence, in cadaver-derived valves preparedfor grafting these important componentsmay already be low or absentat the time of implantation. In allografts explantedafter severaIyears, any original donor cells which have survived in the leafletshave usually not maintaineda normal tissuearchitecture. Bearingin mind the possibility that the histology of allograftedvalves which have required replacementmay differ from that of grafts which are still in place and functioning well, the abovefacts neverthelesscast doubt on the alleged importance of pre-implantationcell viability per se for this type of bioprostbesis. Since a percentageof &grafts known to be completely non-viable at implantation have survived for as long as 20-30 years, factors unrelatedto the persistenceof a donor cell population needto be consideredin future research. Supportedby the Health ResearchCouncil of NZ, the Auckland Medical ResearchFoundationand the NZ Lotteries Board.
289